Lycorine derivative effectively inhibits the replication of coronaviruses both in vitro and in vivo  

作　　者：Liang Shen Jianzhong Zhao Ying Xia Junjie Lu Jiali Sun Jian Tang Hui Xing Lijuan Yin Yang Yang Chunhua Wang 

机构地区：[1]Department of Clinical Laboratory,Xiangyang Central Hospital,Affiliated Hospital of Hubei University of Arts and Science,Hubei,China [2]Shenzhen Key Laboratory of Pathogen and Immunity,National Clinical Research Center for Infectious Disease,State Key Discipline of Infectious Disease,Shenzhen Third People’s Hospital,Second Hospital Affiliated to Southern University of Science and Technology,Guangdong,China [3]Department of Clinical Laboratory,Xiangyang No.1 People’s Hospital,Hubei University of Medicine,Hubei,China [4]State Key Laboratory of Food Nutrition and Safety,Key Laboratory of Industrial Microbiology,Ministry of Education,Tianjin Key Laboratory of Industry Microbiology,National and Local United Engineering Lab of Metabolic Control Fermentation Technology,China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry,College of Biotechnology,Tianjin University of Science&Technology,Tianjin,China

出　　处：《hLife》2024年第2期75-87,共13页健康科学（英文）

基　　金：supported by National Natural Science Foundation of China (82002192,32302218);General project of Natural Science Foundation of Hubei Province (2019CFA016,2022CFB539,2022CFD107);Young and Middle-aged Talents Project of Hubei Provincial Education Department (Q20222605);Tianjin Municipal Science and Technology Committee (21JCQNJC01410);China Postdoctoral Science Foundation (2021M702460);Science and Technology Plan (in the field of medical and health care)of Xiangyang (2022YL05B,2022YL12A).

摘　　要：The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.

关 键 词：BROAD-SPECTRUM antiviral drug lycorine derivative Ly-8 

分 类 号：R373[医药卫生—病原生物学]